Nitrofurantoin, Sulfamethizole and Cephalexin Urinary Concentration in Unequally Functioning Pyelonephritic Kidneys

Nitrofurantoin, sulfamethizole and cephalexin peak urinary drug concentrations were studied in patients and non-human primates with unequally functioning pyelonephritic kidneys. The peak urinary drug concentration of the poorly functioning kidney in comparison to the better kidney was greater than its percentage relative blood flow or creatinine clearance but variable in its relationship to creatinine concentration, osmolality and sodium concentration. Although for each unit of creatinine clearance the poorly functioning kidney had a higher peak urinary drug concentration than the better functioning kidney, for each kidney the peak urinary drug concentration seemed to be directly proportional to the creatinine clearance, the drug dosage and the renal mechanisms of drug excretion. Nitrofurantoin in the usual recommended dosage did not reach minimal inhibitory urinary drug concentration below a unilateral creatinine clearance of 20 ml. per minute. Whereas, sulfamethizole and cephalexin reached peak urinary drug concentrations greater than the minimal inhibitory concentration at the lowest studied unilateral creatinine clearance of 4 and 11 ml. per minute, respectively.